Research, Design, Engineering, and Techno-Economic Analysis of Plant-Based Therapeutic Platform

While many deadly, infectious diseases have been eradicated or reduced significantly in developed countries, they still are responsible for a high number of deaths in developing or underdeveloped countries (http://www.who.int/topics/infectious_diseases/en). Clearly, there is a need for continuous scientific improvement to reduce the cost of medicine significantly and make it affordable and available to most—if not all—of the growing population.

Currently, most of the therapeutics, drugs, diagnostic molecules, antibodies, and vaccines out on the market are made of recombinant proteins. These are mainly produced using traditional production platforms, which include mammalian, microbial, and insect cells cultured in stainless steel or single-use disposable bioreactor systems. While these platforms have improved significantly over the past few decades, they remain relatively long and costly processes. Moreover, costs of pharmaceuticals are increasing alongside global inflation. As a result, large number of global population cannot keep up with the rising costs of medicine. Thus, as more products enter the market, there is a growing need for manufacturing processes that can a) respond quickly to new or sudden medical needs, b) offer more rapid drug development, and c) lower drug prices to address emerging markets including less-developed regions of the world.

Plant-based biomanufacturing of therapeutics, a relatively new platform with a small number of commercial-scale facilities, addresses the needs raised by the expanding market. This emerging platform offers advantages of linear scalability, reduced upstream complexity, reduced time to market, and potentially lower capital and operating costs. It is rapidly becoming a commercially acceptable recombinant protein production platform for human therapeutics. To date, tobacco (Nicotiana sp.) hosts have the most established research and development history for therapeutics production, and an extensive number of proteins have been produced using this platform over the last decade. Other promising plant-based production platforms include rice, moss (Physcomitrella patens), common duckweed (Lemna minor), and microalgae.

In order to understand, access, and optimize plant-based biomanufacturing of therapeutics, we used SuperPro Designer® software and data from laboratory-scale and industry-scale plant-based production facilities to design and simulate a large-scale new “greenfield” biomanufacturing facility that uses transient agroinfiltration of Nicotiana benthamiana plants grown hydroponically indoors under light-emitting diode LED lighting for the production of a monoclonal antibody. A manuscript entitled Techno-Economic Analysis of a Transient Plant-Based Platform for Monoclonal Antibody Production containing our results is available online. The simulation model, provided below, can be download, and modified or adapted by others to assess the profitability of alternative designs, to implement different process assumptions, and to help guide process development and optimization.

Current Project

• Several plant-based therapeutics production involving whole plants, plant cells, and plant cell cultures are currently under investigation. These include Ebola antibodies, therapeutic glycoproteins like butyrylcholinesterase (BChE), and anthrax decoy protein (CMG2-Fc).
• The purpose of these projects is to lower capital and operating costs while expanding production capacity. We aim to make healthcare deliveries affordable to enable wider access to medicines and to improve global health, especially to many of the world’s underprivileged.
• The base case SuperPro Designer^® upstream and downstream processing models developed for the manuscript entitled Techno-Economic Analysis of a Transient Plant-Based Platform for Monoclonal Antibody Production can be downloaded here:
  Download Plant-Made mAb Techno-Economic Analysis SuperPro Designer^® Models

Activities/Involvement

• Our current activity includes designing synthetic gene construct for research scale production of different therapeutic proteins and antibodies and analyze the cost of goods.
• We want to improve fundamental understanding of in vitro enzymatic processes for modifying glycans on glycoproteins, and of the effects of glycan structures on the glycoprotein structure, stability, oligomerization, immunogenicity, and efficacy of therapeutic bioscavengers.
• We will also investigate different methods to achieve ideal starting glycoforms, free of non-human glycans, using plant-based production systems.